A major international consortium co-led by Penn Medicine has received a $12 million National Institute of Mental Health (NIMH) grant for a large-scale genetics study investigating why patients with chromosome 22q11.2 deletion syndrome have an increased risk of schizophrenia and other psychiatric disorders.

Co-directed by Raquel E. Gur, director of the Neuropsychiatry Program at the Perelman School of Medicine at the University of Pennsylvania, the International Consortium on Brain and Behavior in 22q11.2 Deletion Syndrome brings together top researchers and clinicians from 22 institutions, including Penn Medicine and The Children’s Hospital of Philadelphia (CHOP) and five genotyping sites, across North America, Europe, Australia and South America.

With the four-year grant from the NIMH, part of the National Institutes of Health, the Consortium will study the genetic causes behind the high rates of schizophrenia and other psychiatric disorders in those with deletion syndrome, a multisystem disorder that includes birth defects and developmental and behavioral differences across the life span. Such findings may also help identify pathways leading to schizophrenia in the general population in a way that will inform new treatments.

“The funding from the NIH will provide us with the opportunity to advance the understanding of this under-recognized neurogenetic condition,” said Dr. Gur. “The knowledge generated can provide a window to the brain that will benefit millions throughout the world.”

Co-directing the overall consortium with Dr. Gur is Donna McDonald-McGinn, program director of the “22q and You Center” at CHOP. They frequently collaborate on chromosome 22q research, as the principal investigators of the project’s sites at their respective institutions.

Found in approximately 1 in 4,000 live births, 22q11.2 deletion syndrome has many possible signs and symptoms that can affect almost any part of the body, including heart abnormalities that often require surgery in the newborn period, an opening in the roof of the mouth, trouble fighting infection due to a poorly functioning immune system, seizures due to low calcium and significant feeding and swallowing issues. In contrast, some individuals with the 22q11.2 deletion have none of these medical issues. However, most children have developmental delays including delayed acquisition of motor milestones, learning disabilities and significant delays in emergence of language. Moreover, some children have autistic spectrum disorder, ADHD and anxiety.

When entering adolescence or young adulthood, around 25 to 30 percent of patients are at risk of developing schizophrenia, much higher than the one percent rate in the general population.

The Consortium sites have extensive experience in applying integrative genomic and brain-behavior strategies to study individuals with deletion syndrome and schizophrenia and together have provided data on 1,000 genetically and phenotypically characterized individuals with the syndrome, the largest such available sample to date.

“The project is an unprecedented international initiative to examine a common deletion associated with schizophrenia and elucidate its genomic and behavioral substrates,” said Dr. Gur.

Ms. McDonald-McGinn added: “Not only does this successful application demonstrate the genuine commitment on the part of the National Institute of Mental Health to better understand the brain and psychiatric illness, but it highlights the need for such international collaborations. In this instance, 22 clinical and five basic science collaborating sites, all with extremely dedicated clinicians and researchers who have overcome the challenges of differing cultures, languages, time zones and healthcare systems, are working toward the common goal of improving patient care and long-term outcome.”

In addition to Penn Medicine and the “22q and You Center” at CHOP, participating academic sites in the United States include New York’s Albert Einstein College of Medicine, Duke University, Emory University, SUNY Syracuse, UCLA and UC Davis; with sites in Canada (Toronto), Europe (Leuven, Belgium; Marseille, France; Dublin, Ireland; Rome, Italy; Utrecht and Maastricht, the Netherlands; Mallorca and Madrid, Spain; Geneva, Switzerland; Cardiff and London, United Kingdom); Tel Aviv, Israel; Australia (Newcastle); and Chile (Santiago)